Keto Aldonic Acids

The 2-keto-3-deoxy-aldonic acid (phosphate) aldolases from Pseudomonas strains - 3-deoxy-2-keto-L-arabonate (F.C 4.1.2.18), 3-deoxy-2-keto-D-xylonate (EC 4.1.2.28), 3-deoxy-2-keto-6-phospho-D-gluconate (EC 4.1.2.14) and 3-deoxy-2-keto-6-phospho-D-galactonate aldolase (EC 4.1.2.21) - appear to be specific even for the acceptor components, but allow stereoselective syntheses of the respective natural substrates29. 

Pyruvate-dependent lyases serve catabolic functions in vivo in the degradation of sialic acids and KDO (2-keto-3-deoxy-manno-octosonate), and in that of 2-keto-3-deoxy aldonic acid intermediates from hexose or pentose catabolism. 

Several mechanisms have been proposed for the cleavage reactions. One involves formation of an osone from the 1,2-enediol, followed by oxidation to a 2-keto-aldonic acid, which in turn gives the next lower... 

In vivo, pyruvate lyases perform a catabolic function. The synthetically most interesting types are those involved in the degradation of sialic acids or the structurally related octulosonic acid KDO, which are higher sugars typically found in mammalian or bacterial glycoconjugates [62-64], respectively. Also, hexose or pentose catabolism may proceed via pyruvate cleavage from intermediate 2-keto-3-deoxy derivatives which result from dehydration of the corresponding aldonic acids. Since these aldol additions are freely reversible, the often unfavourable equilibrium constants require that reactions in the direction of synthesis have to be driven by an excess of one of the components, preferably pyruvate for economic reasons, in order to achieve a satisfactory conversion. 

Comparable to the situation for the sialic acid and KDO lyases (vide supra), sets of stereochemically complementary pyruvate lyases are known, e,g. in Pseudomonas strains, which act on related 2-keto-3-deoxy-aldonic acids [112]. The enzymes cleaving six-carbon sugar acid phosphates—the KdgA and 2-keto-3-deoxy-6-phospho-D-galactonate (20) aldolases (KDPGal aldolase EC 4.1.2.21) [139] — are typified as class I enzymes, whereas those acting on non-phosphorylated five-carbon substrates — 2-keto-3-deoxy-L-arabonate (21) (KDAra aldolase EC 4.1.2,18) [140, 141] and 2-keto-3-deoxy-D-xylonate (22)... 

This section deals with acids, that are formally modified aldonic acids, such as keto, deoxy, and branched-chain acids (including the so-called saccharinic acids). The aminoaldonic acids, which are oxidation products of amino sugars, and, in particular, the important nonulosaminic acids (neuraminic acids) and muramic acid, are not discussed here. The formation of saccharinic acids by the treatment of sugars with alkali, and the mechanisms involved, are likewise outside the scope of this chapter. 

A. Abbadi and H. van Bekkum, Highly selective oxidation of aldonic acids to 2-keto-aldonic acids over Pt-Bi and Pt-Pb catalysts, Appl. Catal. A, 124 (1995) 409 117. 

Calcium D-galactonate, I, 70 Calcium D-gluconate, III, 141, 142, 149, 152, 155, 156, 161 IV, 331 Calcium hypochlorite, III, 165 Calcium 2-keto-D-gIuconate, III, 148, 155 Calcium 5-keto-D-gluconate, III, 156 Calcium lactobionate, calcium bromide double salt, III, 155 Calcium Ievulinate, IV, 311 Calcium maltobionate, III, 161 Calcium D-mannonate, III, 152 Calcium pectate, I, 334 Calcium D-rhamnonate, III, 144 Calcium salts, in preparation of aldonic acids with NaCN, I, 23 Calcium vicianobionate, III, 154 Calcium D-xylonate, III, 155 Camphor, optically active, formed from inactive (racemic) camphor carboxylic acid in the presence of quinine, quinidine or nicotine, V, 53 Camphor carboxylic acid. See Camphor. Camphor, 3-hydroxy-, IV, 89 Camphorquinone, phytochemical reduction of, IV, 89... 

Further oxidation of the aldonic acids results in the formation of either 2-keto or 5-keto aldonic acids (XII and XIII). After this step, degradation of the carbon chain apparently occurs. This degradation also occurs normally vdth ketoses (IV), a trihydroxybutyric acid (XVIII) being the main degradation product. 

The oxidation of uronic acids (VIII) leads to the formation of saccharic acids (XIV) mild conditions are necessary to avoid damaging the sensitive uronic acid grouping. In a similar manner, osones (VII) may be converted to 2-keto aldonic acids (XII). 

Oxidation of the primary alcohol group on C6 has been noted in a few cases. A small yield of saccharic acid (XIV) has been obtained in the formation of an aldonic acid from an aldose. In several cases glycosides have been oxidized to glycuronides (XV). More drastic action on the glycoside has led to a splitting of the carbon chain at C2—C3 and C3—C4, with elimination of C3, similar to the action of periodic acid diglycolio acid derivatives (XVI) are formed. The oxidation of the primary alcohol group on C6 of ketoses has occasionally led to the formation of 5-keto acids (XIII). 

Tiemann studied the further oxidation of D-gluconic acid with bromine at 100 a reducing sirup was formed which was isolated as an amorphous barium salt or a crystalline osazone. Ruff repeated the work and could find no oxygluconic acid in the oxidation mixture most of the D-gluconic acid was unaltered and the reducing power was very low, especially in comparison with that obtained when keto aldonic acids were prepared by the action of hydrogen peroxide and ferrous salts. By ether extraction and distillation the formation of formic, oxalic and glycolic acids was shown. 

The oxidation products of L-rhamnose treated with an excess of bromine for five days included a small amount of 5-keto-L-rhamnonic lactone 1000 g. of L-rhamnose gave 550 g. of L-rhamnonic lactone and 55 g. of the keto derivative. In confirmation, Voto6ek and Malachata achieved the partial conversion of L-rhamnonic lactone to the keto derivative. The very low yield, however, is indicative of the slowness of the reaction and the relative stability of the normal aldonic acids or lactones toward further oxidation. 

Everett and coworkers have done extensive work on this overoxidation of aldoses with bromine at 25° for long periods of time (forty to fifty days). Under these conditions, appreciable amounts of the keto acids are obtained. Hart and Everett obtained 5-keto aldonic acids from D-glucose, D-mannose, D-galactose, D-xylose and D-gulonic lactone. The barium salts were isolated and converted to the brucine salts. The structure of the oxidation product from D-xylose was not determined. The stability of these keto acids to further bromine oxidation had been noted earlier by Kiliani. ... 

Another method of preparing keto aldonic acids, those of the 2-keto type, is by oxidation of the corresponding osone. Neuberg and Kitasato obtained 18 g. of calcium 2-keto-D-gluconate from 20 g. of the osone by the action of bromine at 20 . Similarly, 2-keto-n-galactonic and 2-keto-maltobionic acids were prepared by Kitasato. The substances were characterized generally as the brucine salts because of the amorphous nature of the calcium salts. 

The well-known Ruff degradation of aldonic acids to aldoses with one less carbon was first applied with bromine as the oxidant. Calcium D-gluconate was treated with an excess of bromine at 20° for ten hours the acidity of the solution was kept low with lead carbonate. The filtrate was processed and D-arabinose was obtained in small yield as the oxime. However, Ruff found that the effect of hydrogen peroxide was much better and abandoned the use of bromine. Fenton noted the same effect in the oxidation of tartaric acid to dihydroxymaleic acid the action of oxygen was more effective than that of the halogens. It was assumed that a keto aldonic acid was the intermediate in the degradation of the aldonic acid to the new aldose, and the apparent stability of the keto acids to further oxidation by bromine may be the reason for the low yields with this oxidant. 

L-sorbose by the action of bromine. The former product represented only one-third of the reducing material. The stability of the keto aldonic acids to bromine had previously been noted by several workers Kiliani prepared a keto-L-rhamnonic acid which did not react within four days with an excess of bromine. Similar results were reported by Everett, Edwards and Sheppard. ... 

Both chloric and iodic acid have been used as oxidants in acidic solutions. No examples with bromic acid have been reported. Withaldonic acids the primary products are keto acids. However, an example does exist of the conversion of an aldose to an aldonic acid. This might be classed as an indirect or secondary bromine oxidation, since a mixture of sodium chlorate and hydrobromic acid was used in acid solution. 

The carboxylic acids derived from sucrose may find some use in pharmaceutical and agricultural chemistry. The uronic and 2-keto-aldonic acids obtained by hydrolysis of these compounds represent a great industrial... 

Reduction of 1-nitro-l-alkene derivatives such as 65 provided 2-deoxy-aldose oximes and their elimination products such as 66 and 67, respectively (Scheme 11). The oxime 66 could be converted into the corresponding free 2-deoxy-sugar, 2-deoxy-aldononitrile and 2-deoxy-aldonic acid. Radical cyclization of 5-keto-aldose aldoximes to give aminocyclopentitol derivatives is covered in Chapter 18. 

The chemisry of the hexulosyl bromide 20 has beat studied and a facile synthesis of the azidogalactosyl bromide 21 by way of D-galactal triacetate has been outlined. The conversion of 6-bromo-6-deoxyaldonolactones into 3,6-anhydro-aldonic acids is covered in Chapter 16 and the conversion of difructose dianhydride by way of deoxyhalo derivatives into 3,6-anhydro-keto-D-fructose is mentioned... 

By use of hydroxy- and keto-acids as model compounds, the RuflF degradation of aldonic acids with hydrogen peroxide and iron(iii) has been examined, and the pathway illustrated in Scheme 1 proposed. A remaining difficulty. 

The aldonyl chlorides can be prepared 32) by treatment of acetylated aldonic acids with PCU. These chlorides are used for the preparation of open-chain derivatives of aldoses by catalytic reduction with hydrogen in xylene solution 33), Keto acetates with one carbon atom more than the aldonyl chloride are formed by the action of diazomethane. Acetic acid removes the diazo group. In this manner, L-fructose was made from L-arabonic acid 34). 

Keto and 5-keto aldonic acids also give carbon dioxide and furfural (see below) in yields similar to those for the uronic acids. However, ascorbic acid, as discussed later, gives a very high yield (above 80%) of furfural. Reductic acid, an enolic substance similar in structure to the ascorbic... 

The keto aldonic acids of the hexose series are of the 2- and 5-keto types. The 2-keto acids have been called osonic acids because of their preparation by the oxidation of osones. The 5-keto acids have been termed keturonic... 

The similarity of the keto aldonic acids and uronic acids has been mentioned earlier. 2-Ketogluconic acid gives a 33 % yield of furfural in 4 hours and the 5-keto acid 42.5%, when heated with 12% hydrochloric acid ISO), The evolution of carbon dioxide from the 5-keto acid is quantitative. 

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